Our previous results indicated that the organotropic effects of methylazoxymethanol (MAM) are due to its metabolism by NAD plus/NADP plus-dependent dehydrogenase enzymes present in the sensitive organs. Pyrazole, an inhibitor of alcohol dehydrogenase, inhibits the acute lethal effects of MAM, suggesting that the activating dehydrogenase enzyme was alcohol dehydrogenase. To determine whether the active metabolite was the aldehyde derivative of MAM or the acid derivative which could be expected to be subsequently formed, we treated animals with disulfiram, an inhibitor of aldehyde dehydrogenase. Acute effects of MAM in animals pretreated with disulfiram were potentiated, suggesting that the aldehyde was in fact the active metabolite. The effects of pyrazole on the incidence of MAM acetate-induced tumors were studied. Animals were pretreated with pyrazole 2 hours prior to their receiving MAM acetate. Pyrazole prevented the induction of intestinal tumors. Tumors of the kidney, skin and Zymbal's gland were now observed. These tumors may now be appearing because, with protection against acute toxicity afforded by pyrazole, higher doses of MAM acetate could be given. Dimethylhydrazine (DMH) induces intestinal tumors in Sprague-Dawley rats but not in Lobund Wistar rats. This difference could be due to the inability of Lobund Wistar rats to metabolize DMH. In collaboration with Dr. Morris Pollard (Univ. of Notre Dame), we studied the incidence of tumors in both stocks of rats treated with MAM acetate, the end product of DMH metabolism. Colon tissue in both stocks of rats had similar NAD plus-dependent dehydrogenase activities; still a sevenfold greater incidence of colon tumors was found in the Sprague-Dawley rats. The results indicated that the difference in susceptibility to colon tumor induction between the rat stocks was partially related to metabolic activation of the DMH and to other, as yet undertermined endogenous factors.